Endothelin (ET), a recently discovered peptide, has been found to be the most potent vasoconstrictor known to men. It is found in high amounts in the urine compared to low levels in the plasma. Although much has been learned about the structure and biological effects of ET, little is known about the regulation of its urinary excretion (UETV). We are investigating 1) the effects of angiotensin II (AII) and Phenylephrine (PHE) on the UETV in normal volunteers. We started AII infusion at a rate of 3 ng/kg/min and titrated to an increase in mean arterial blood pressure of at least 20 mmHg for 60 minutes. The amount of AII required averaged 11.7 ng.kg/min. After a washout period, PHE was started at a rate of 1 mug/kg/min and titrated to same target blood pressure. The average PHE required was 2.5 mug/kg/min. AII roughly doubled urine flow (UV) and UETV in the initial 30 minutes, dropping back to baseline level in the last 30 minutes. PHE roughly increased urine flow by 8 fold and UETV by 7 fold in the first 30 minutes returning to close to baseline in the final 30 minute period.